The serotonin receptors, also known as 5-hydroxytryptamine (5-HT) receptors are a group of G protein-coupled receptors (GPCRs) and ligand-gated channels found in the central and peripheral nervous system. The serotonin receptors are activated by serotonin, which is a neurotransmitter and a neuromodulator of the central nervous system. The 5-HT receptors have been grouped into several main classes. Among these main classes, the 5-HT1 class comprises receptors characterized by a high affinity for serotonin. The 5-HT1 class is itself divided into a subclass of receptors whose pharmacological characteristics and regional distributions in the central nervous system are distinct.
The 5-HT1A receptor is the most widespread of all the 5-HT1 receptors. In the central nervous system, 5-HT1A receptors exist in the cerebral cortex, hippocampus, septum, amygdala, and raphe nucleus in high densities, while low amounts also exist in the basal ganglia and thalamus. 5-HT1A receptor agonists are involved in neuromodulation, decreasing blood pressure and heart rate via a central mechanism, by inducing peripheral vasodilation, and by stimulating the vagus nerve. Activation of central 5-HT1A receptors triggers the release or inhibition of norepinephrine. 5-HT1A receptor agonists show efficacy in relieving anxiety and depression.
Befiradol [(3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl)-amino]-5 methyl}piperidin-1-yl]methanone; CAS #208110-64-9] is a selective and high efficacy serotonin 5-HT1A receptor agonist (U.S. Pat. Nos. 6,020,345; 7,208,603).

Befiradol has been suggested as a treatment for depression, anxiety, and pain. More recently, befiradol has been under investigation in the treatment of movement disorders including Parkinson's disease, Huntington's disease, Tourette's syndrome, dystonia, L-DOPA-induced dyskinesia, and tardive dyskinesia (WO 2016/005527).
Befiradol, however, is metabolized in the liver and is likely subject to extensive cytochrome P450-mediated oxidative metabolism. Befiradol is likely metabolized predominantly by N-dealkylation.
Adverse effects associated with befiradol may include dizziness, light-headedness, headache, nausea, somnolence, insomnia, tachycardia, dry mouth, diarrhea, rash, and the like. Additionally, some metabolites of befiradol may have undesirable side effects.
Accordingly, there is a need for 5-HT1A receptor agonists with improved pharmacokinetic properties.